Home cage pretreatment with diazepam: effects on subsequent conflict testing and rotorod assessment

In various anxiolytic tests, benzodiazepines produce a maximal anxiolytic response only upon repeated treatment. The question arises as to whether repeated treatment produces an increase in anxiolytic efficacy or a decrease in another benzodiazepine-mediated effect (i.e., muscle relaxation/sedation) that functions to attenuate the full expression of the anxiolytic response. To address this issue, rats were pretreated in their home cages with either vehicle, diazepam or CGS 9896 (a nonsedating, non-muscle relaxant partial benzodiazepine agonist with anxiolytic efficacy) and challenged, 7 days later, with either diazepam or CGS 9896 in either a conflict (anxiolytic efficacy) or a rotorod (muscle relaxant/sedative effects) procedure. Rats who first experienced diazepam in the test situation (vehicle home cage pretreatment) showed only a moderate anxiolytic response and a compromised motor response. Pretreatment with diazepam in the home cage produced a tolerance to the motor-decreasing effects of diazepam and induced a maximal anxiolytic effect upon first challenge with diazepam in the test situation. CGS 9896, on the other hand, produced a maximal anxiolytic effect regardless of home cage pretreatment. Home cage pretreatment with CGS 9896 did not obviate the muscle relaxant/sedative or submaximal anxiolytic effects of diazepam, suggesting that repeated exposure to an anxiolytic effect is not the underlying basis for the repeated benzodiazepine treatment phenomenon. Rather, the motor-impairing effects of the benzodiazepines cause the submaximal response noted upon first exposure to these drugs in the anxiolytic test situation. This effect tolerates, leaving the expression of the maximal response.